Prinzmetal's or Prinzmetal angina (/ˈprɪntsmɛtəl/, sounds like "prints metal") (also known as variant angina, angina inversa, or coronary vessel spasm) is a syndrome typically consisting of angina (cardiac chest pain) at rest that occurs in cycles. It is caused by vasospasm, a narrowing of the coronary arteries caused by contraction of the smooth muscle tissue in the vessel walls rather than directly by atherosclerosis (buildup of fatty plaque and hardening of the arteries).

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Symptoms typically occur at rest, rather than on exertion (thus attacks usually occur at night).[1] Two-thirds of patients have concurrent atherosclerosis of a major coronary artery, but this is often mild or not in proportion to the degree of symptoms.

Prinzmetal's should be suspected by a cardiologist when the pain occurs at rest and/or in clusters, and in the absence of a positive treadmill stress test, as Prinzmetal's is exercise tolerant and can generally only be diagnosed after other forms of cardiac disease have been ruled out.

It is associated with specific ECG changes (elevation rather than depression of the ST segment). However, in order to be diagnosed, these ECG changes can only be tracked when the electrocardiogram occurs while the patient is experiencing an attack. Therefore, many experts recommend provocative testing during Electrocardiogram testing to attempt to induce an attack when Prinzmetal's is suspected.

The mechanism that causes such intense vasospasm, as to cause a clinically significant narrowing of the coronary arteries is so far unknown. There are three relevant hypotheses:

Enhanced contractility of coronary vascular smooth muscle due to reduced nitric oxide bioavailability caused by a defect in the endothelial nitric oxide synthetase enzyme which leads to endothelial function abnormalities.[2][3]

Acetylcholine is normally released by the parasympathetic nervous system (PSNS) at rest, and causes dilation of the coronary arteries.[4] While acetylcholine induces vasoconstriction of vascular smooth muscle cells through a direct mechanism, acetylcholine also stimulates endothelial cells to produce nitric oxide (NO). NO then diffuses out of the endothelial cells, stimulating relaxation of the nearby smooth muscle cells. In healthy arterial walls, the overall indirect relaxation induced by acetylcholine (via nitric oxide) is of greater effect than any contraction that is induced.

When the endothelium is dysfunctional, stimulation with acetylcholine will fail to produce, or produce very little, nitric oxide. Thus, acetylcholine released by the PSNS at rest will simply cause contraction of the vascular smooth muscle.

Thromboxane A2, a vasoconstrictor released by platelets to aid in clot formation, may also play a role in Prinzmetal's angina. Lipoprotein(a) interferes with fibrinolysis by competing with plasminogen. The impaired fibrinolysis triggers thrombus formation, which also results in coronary vasospasm in variant angina.[5][6]

Although Prinzmetal's Angina has been documented in between 2% to 10% of angina patients, it can be overlooked by cardiologists who stop testing protocol after ruling out typical angina. Rarely, an EKG can capture diffuse ST elevations.

The gold standard is coronary angiography with injection of provocative agents into the coronary artery. Rarely, an active spasm can documented angiographically (e.g. if the patient receives an angiogram with intent of performing a primary coronary intervention with angioplasty). Depending on the local protocol, provocation testing may involve substances such as ergonovine, methylergonovine or acetylcholine. Exaggerated spasm is diagnostic of Prinzmetal angina.